Rizvi SA, Tereshko V, Kossiakoff AA, Kozmin SA
J. Am. Chem. Soc. 2006 Mar;128(12):3882-3
PMID: 16551075
Abstract
Bistramide A is a highly potent antiproliferative marine natural product from Lissoclinum bistratum. We have previously established actin as the primary cellular receptor of bistramide A. We report herein the X-ray structure of bistramide A bound to monomeric actin at a resolution of 1.35 A. The most notable aspect of the bistramide A-actin structure is an extensive hydrogen-bonding network established upon a deep penetration of the central segment of bistramide A into the actin-binding cleft between subdomains 1 and 3. The structure presents the first insight into the observed ability of bistramide A to modulate G-actin polymerization. The structural information combined with our ability to chemically modify the bistramide framework provides the basis for rational development of a series of new synthetic analogues as useful probes for studying actin cytoskeleton and as potential therapeutic leads.